Format

Send to

Choose Destination
Nat Med. 2018 Jun;24(6):724-730. doi: 10.1038/s41591-018-0040-8. Epub 2018 Jun 4.

Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.

Author information

1
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
2
Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
3
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. sar@mail.nih.gov.

Abstract

Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1-7. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers8-11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.

PMID:
29867227
DOI:
10.1038/s41591-018-0040-8

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center